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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 721 records · Page 40Linked to original sources
PubMed1982

Laparoscopic findings of the liver in the diagnosis of primary biliary cirrhosis: "reddish patch", a laparoscopic feature in the asymptomatic stage.

The laparoscopic findings of the livers of 12 patients with primary biliary cirrhosis (PBC), including six asymptomatic and six symptomatic cases, were investigated. On the liver surface of asymptomatic PBC, we found a laparoscopic appearance, consisting of reddish patches of irregular shape, ranging from 0.5 to 3 cm in diameter, and not evenly distributed. Five of six cases of asymptomatic PBC had reddish patches in our series. From serial laparoscopic observations, the patches were found to lose some of their reddish tone and to develop protuberances with vaguely outlined white markings in each reddish areas. The protuberances and white markings are characteristic appearances of the liver surface in more advanced PBC cases. The transition of reddish patches to protuberances with white markings coincided with progression among histopathological stages in PBC classified by Scheuer. A histometrical examination showed that areas with reddish patches had less advanced changes of intrahepatic bile ducts. As a result, we propose that laparoscopic findings of the liver have a value in the diagnosis of PBC and "reddish patch" is considered a laparoscopic feature which has no been described in asymptomatic PBC.

Adult↗
PubMed1982

Increased norepinephrine content in diabetic rat heart.

In an attempt to clarify the mechanism of cardiac neuropathy in diabetes mellitus, Wister male rats were made diabetic by streptozotocin injection for 11 to 13 weeks, and catecholamine concentrations of hearts were determined by high performance liquid chromatography. No apparent histological changes were found in hearts and kidneys of any group of rats. Controls used were age-matched normal rats and Goldblatt-hypertensive rats, because streptozotocin induced diabetic rats appeared to be significantly hypertensive. Heart norepinephrine concentrations of diabetic rats and diabetic-Goldblatt-hypertensive rats were markedly higher (8,380 +/- 300 pmol/g tissue and 6,980 +/- 390, respectively) compared with those of controls and Goldblatt-hypertensive rats (2,700 +/- 470 and 2,010 +/- 300, respectively). These results suggest some disturbances in catecholamine secretion in diabetic hearts before typical microangiopathic changes take place.

Animals↗
PubMed1982

Role of calmodulin in platelet aggregation. Structure-activity relationship of calmodulin antagonists.

Two series of derivatives of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), including a dechlorinated analog of W-7 (W-5) and various aminoalkyl chain analogs of W-7 (A-3, A-4, A-5, I-240, A-6) were synthesized and their structure-activity relationships with calmodulin antagonistic actions and their potencies in inhibiting human platelet aggregation in vitro were investigated. Their binding affinities to calmodulin in the presence of 100 microM Ca2+ were dependent both on the chlorination of the naphthalene ring and on the length of aminoalkyl chain. The ability of these derivatives to inhibit Ca2+-dependent phosphorylation of 20,000-dalton myosin light chain from platelets correlated well with the magnitude of their binding affinity to calmodulin. W-7(10-100 microM) inhibited in a dose-dependent manner platelet aggregation induced by collagen (2 micrograms/ml), ADP (5 microM), epinephrine (1 microgram/ml), sodium arachidonate (0.83 mM), thrombin (0.125 U/ml), and A-23187 (10 microM). The IC50 value (concentration producing 50% inhibition of aggregation) of W-7 was lower in arachidonate- and collagen-induced aggregation than in ADP- or epinephrine-induced aggregation. A good correlation between the potency in inhibition of collagen-induced aggregation by W-7 and its derivatives and their affinities to calmodulin was obtained (r = 0.94). Thus, the inhibitory mechanism of these compounds may be due to their effect on Ca2+-calmodulin-dependent processes, such as 20,000-dalton myosin light chain phosphorylation. These data also support the hypothesis that the calmodulin-mediated system has an important role in platelet function.

Actomyosin↗
PubMed1982

High affinity 3,5,3'-L-triiodothyronine binding to synaptosomes in rat cerebral cortex.

Studies were undertaken to define the existence of specific T3-binding sites in the synaptosomal fraction of rat cerebral cortex. Development-related changes of the synaptosomal T3-binding sites were compared with those of nuclear T3 receptors in rat cerebral cortex. Scatchard analysis was compatible with the existence of two sets of high affinity T3-binding sites: K1, with a mean (+/- SE) apparent dissociation constant (Kd) of 3.22 +/- 0.63 x 10(-11) M and a mean (+/- SE) maximum binding capacity (MBC) of 3.2 +/- 0.3 pg T3/mg protein, and K2, with a K4 of 2.64 +/- 0.15 x 10(-9) M and a MBC of 218.3 +/0 15.0 pg T3/mg protein. When compared to T3, 27-, 135-, 500-, and 1000-fold higher concentrations of T4, 3,5-diiodothyronine (3,5-T2), triiodothyroacetic acid, and rT3, respectively, were needed to obtain 50% depression of the synaptosomal T3 binding. Tetraiodothyroacetic acid, 3,3'-T2, 3'5'-T2, 3-monoiodothyronine (3-T1), 3'-T1, and thyronine had little effect. The MBC of T3 nuclear receptors was the highest at 2 days of age and significantly decreased thereafter, although an almost constant K4 was observed in all age groups studied. On the contrary, the MBC of the higher affinity synaptosomal T3-binding sites was low in 2-day-old rats (20.3 +/- 1.2 pg T3/g tissue) and increased thereafter to the level in young adult ras (50.4 +/- 2.2 pg T3/g tissue). However, the Kd of synaptosomal T3-binding sites was also unchanged in all age groups studied. These findings clearly indicate that there exist specific T3-binding sites in synaptosomes from rat cerebral cortex.

Aging↗
PubMed1982

Sequential deiodination of thyroxine in human thyroid gland.

The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs. Sequential deiodination of T4 to 3,3'-T2 was also recognized in normal human thyroid glands. These iodothyronine deiodinations were dependent on incubation time, tissue volume, temperature, pH, and concentration of dithiothreitol. The monodeiodination of rT3 to 3,3'-T2 proceeded very rapidly and the maximal production of 3,3'-T2 was obtained at about 5 min. In the other reactions, the products accumulated in an almost linear fashion during the period of 60 min. The optimal pH for 5-monodeiodination was 9.0, while that for 5-monodeiodination was 5.5-6.5. In the absence of dithiothreitol, all of these reactions were abolished. Propylthiouracil and iopanoic acid inhibited the reactions, whereas methimazole and potassium iodide had no effect. Kinetic study revealed that the apparent Km and maximum velocity of the conversion of T3 to 3,3'-T2 were 10.9 microM and 19 pmol 3,3'-T2/mg protein.min, respectively, and that those of rT3 to 3,3'-T2 were 0.37 microM and 80 pmol 3,3'-T2/mg protein.min, respectively. There was a significant difference in the conversion of T4 to rT3 between normal [0.56 +/- 0.04 pmol/mg protein.min (mean +/- SE)] and Graves' thyroids 0.88 +/- 0.06 pmol/mg protein min). Moreover, a significant difference was found between 3,3'-T2 production rate from T3 or rT3 in the Graves' thyroids and that in the normal thyroids. The overall reaction from T4 to 3,3'-T2 in the Graves' thyroids (4.04 +/- 0.70 pmol/mg protein.min) was significantly higher than that in the normal thyroids (0.63 +/- 0.11 pmol/mg protein.min; P less than 0.001). The results indicate the existence of 5-deiodinase that produces rT3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from rT3 in human thyroids. Accelerated conversion of T4 to 3,3'-T2 via either T3 or rT3 was observed in Graves' thyroid glands.

Diiodothyronines↗
PubMed1982

Decreased response of plasma catecholamine to stress in diabetic rats.

Previously we reported that the heart norepinephrine concentration was markedly increased in diabetic rats. To further study the relationship between a disturbance in the autonomic nervous system and catecholamine metabolism in diabetes mellitus, the plasma catecholamine response to stress and catecholamine concentration of heart and adrenals were measured. Wistar male rats were made diabetic by streptozotocin and kept for 13 weeks. A silicon catheter was placed in the superior V. cava 1 week prior to the experiment. Insulin was injected subcutaneously for 3 days once daily. After an overnight fast and without anesthesia, 1 ml of blood, a control sample, was obtained and then the animals were exsanguinated. The blood was mixed with 1 mM EGTA at a final concentration and centrifuged. The tissue was homogenized with 0.4 N perchloric acid containing 1 mM EGTA and centrifuged at 10,000 x g for 20 minutes. Catecholamines were determined by high performance liquid chromatography. Normal rats responded to blood withdrawal stress, and plasma catecholamines were markedly increased, but almost no increase or an actual decrease was observed in diabetic rats. These abnormal responses were improved by insulin treatment. Heart norepinephrine was increased significantly in the diabetic rats compared with the control rats and was reduced significantly by insulin injections. Adrenal epinephrine was also significantly increased in the diabetic rats compared with the control rats, but was not significantly reduced by insulin. These result suggest a possible disturbance of catecholamine secretion in the diabetic rats.

Adrenal Glands↗
PubMed1982

Characteristics of rT3 5'-monodeiodination in rat brain: comparison with T4 and T3 5-monodeiodinations.

The present study revealed the existence and some characteristics of rT3 5'-deiodinase in rat brain by measuring the production of 3,3'-T2 from rT3 by radioimmunoassay. The conversion of rT3 to 3,3'-T2 was dependent on the duration of the incubation, tissue amount, temperature and pH (the optimal pH was 8.0), suggesting its enzymatic nature. Apparent Km was estimated to be 0.16 microM and the Vmax was 139.3 fmol/mg protein/min. The converting activity was dependent on the concentration of dithiothreitol (DTT). In contrast to T4 or T3 5-deiodinase, rT3 5'-deiodinase activity in the rat brain was the highest in cerebellum and the activity was low in the neonatal rat brain. Moreover, the 5'-deiodinase activity was inhibited by propylthiouracil (PTU). These differences between rT3 5'-deiodinase and T4 or T3 5-deiodinase suggest that different deiodinases are present in rat brain, and the local conversion of thyroid hormone is important for its action in the central nervous system.

Age Factors↗
PubMed1981

A case of chronic veno-occlusive disease of the liver.

A case of chronic veno-occlusive disease of the liver manifested by ascites in a 59-year-old Japanese male is described. The patient had not been exposed to pyrrolizidine alkaloids, but had been receiving allopurinol for hyperuricemia, the only drug taken throughout the period in which the hepatic lesion developed. The hepatic veins and inferior vena cava were patent according to angiography. The first biopsy showed histological characteristics of the disease and the following two biopsies demonstrated the progression of the hepatic lesion from central fibrosis to non-portal cirrhosis. Morphometric analysis of the sublobular and central veins in the three serial biopsy specimens demonstrated stepwise decrease of the ratio of the veins per portal triad and stepwise increase of severely obliterative veins.

Allopurinol↗
PubMed1981

Inner ring monodeiodination of thyroxine and 3,5,3'-L-triiodothyronine in rat brain.

To elucidate the metabolism of thyroid hormone in the central nervous system (CNS), 5-monodeiodinating activities were studied by incubating T4 or T3 with an aliquot of the P2 fraction of the rat brain in the presence of dithiothreitol and measuring the amounts of rT3 or 3,3'-L-diiodothyronine (3,3'-T2) produced by RIA. The production of rT3 or 3,3'-T2 was dependent upon duration of the incubation, amount of tissue used, temperature, and pH (the optimal pH was 8.0). These findings show that these reactions are enzymic in nature. For the conversion of T4 to rT3, the Km was estimated to be 1.33 microM, and the Vmax was 173 fmol/mg protein . min. For the conversion of T3 to 3,3'-T2, the Km was estimated to be 2.31 microM, and the Vmax was 94 fmol/mg protein . min. Both the conversion of T4 to rT3 and that of T3 to 3,3'-T2 were dependent on the concentration of dithiothreitol, but were not inhibited by propylthiouracil, the well known inhibitor of 5'-deiodinating activity. Both activities were mainly found in the synaptosomal fractions. The P2 fraction from fetal and neonatal rat brains had significantly higher activity than that from the adult brain. These findings demonstrate the presence of 5-monodeiodinating activities in the rat brain.

Aging↗
PubMed1981

Reversible changes of the histological abnormalities of the thyroid in patients with painless thyroiditis.

The histological abnormalities on percutaneous needle biopsy of the thyroid were investigated in two patients (cases 1 and 2) with transient thyrotoxicosis and low radioactive iodine uptake by the thyroid and in a patient (case 3) with transient hypothyroidism which might be the consequence of transient thyrotoxicosis. The most characteristic findings of lymphocytic thyroiditis, such as extensive lymphocyte infiltration with collapsed follicles and degeneration of follicular cells of the thyroid, were found in case 1, in whom the thyroid biopsy was performed in the thyrotoxic phase. Ashkanazy cells were not present and fibrosis was not observed in this specimen. Histological examination of the thyroid biopsy specimen, which was obtained in the recovery phase in case 1, revealed well preserved thyroid follicles and slight lymphocytic infiltration. In addition, papillary infoldings of cuboidal epithelium were found in cases 2 and 3, in whom the thyroid biopsy was done in the hypothyroid phase. The follow-up biopsy of the thyroid was performed in the recovery phase in case 3. The biopsy specimen showed focal lymphocytic infiltration and the follicles lined by low cuboidal cells without papillary infoldings. In all biopsy specimens, there was no evidence of subacute thyroiditis, as characterized by granulomatous changes and breakdown of colloid follicles with foreign body giant cell reaction. The present findings revealed that the histological abnormalities, such as lymphocytic infiltration and follicular epithelial changes of the thyroid, observed in the patients with painless thyroiditis, can improve spontaneously during the course of several months.

Adult↗
PubMed1981

Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man.

To evaluate the effects of aging on T4 metabolism, serum 3,3'diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronine (3,5-T2) as well as T4, T3, and rT3 concentrations were determined by RIAs in 81 normal subjects, aged 24-81 yr. 3,3'-T2, 3',5'-T2, and 3,5-T2 antisera were prepared by immunizing rabbits with the protein conjugate of each diiodothyronine. Since the 3',5'-T2 antiserum cross-reacted with rT3 to the extent of 1.8%, correction was made by subtracting 1.8% of the rT3 value from the measured 3',5'-T2 value. The other 2 antisera had no noticeable cross-reactivity with various thyroid hormone derivatives. Although no significant relation existed between T4 levels and age (r = -0.14; P greater than 0.1) serum T3 showed a significant correlation with age (r = -0.28; P less than 0.05). In contrast, no significant correlation was observed between rT3 and age (r = 0.12; P greater than 0.1). Serum 3,3'-T2, 3',5'-Tw, and 3,5-T2 values (nanograms per dl) all had significant inverse correlations with age, the coefficients of correlation being -0.38 for 3,3'-T2 (P less than 0.01), -0.58 for 3',5'-Tw (P less than 0.01), and -0.47 for 3,5-T2 (P less than 0.01). These findings suggest that sequential monodeiodinating activities in T4 metabolism decrease with increasing age.

Adult↗
PubMed1981

Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue.

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.

Adenoma↗